Blood DNA methylation signatures of lifestyle exposures: tobacco and alcohol consumption.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36443762", "kind": "science-record", "revision": 2, "content_hash": "sha256:a3fdbe1cce851655f75e0ac794c197f7f9b96cdac2cfb61e8e6a37c852bdd75d", "created_at": "2026-11-01T19:00:55Z", "updated_at": "2026-11-01T21:29:33Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Blood DNA methylation signatures of lifestyle exposures: tobacco and alcohol consumption.", "doi": "10.1186/s13148-022-01376-7", "pmid": "36443762", "authors": ["Jonviea D Chamberlain", "Sébastien Nusslé", "Laurence Chapatte", "Cassandre Kinnaer", "Dusan Petrovic", "Sylvain Pradervand", "Murielle Bochud", "Sarah E Harris", "Janie Corley", "Simon R Cox", "Semira Gonseth Nusslé"], "journal": "Clinical epigenetics", "year": 2022, "abstract": "BACKGROUND: Smoking and alcohol consumption may compromise health by way of epigenetic modifications. Epigenetic signatures of alcohol and tobacco consumption could provide insights into the reversibility of phenotypic changes incurred with differing levels of lifestyle exposures. This study describes and validates two novel epigenetic signatures of tobacco (EpiTob) and alcohol (EpiAlc) consumption and investigates their association with disease outcomes.\nMETHODS: The epigenetic signatures, EpiTob and EpiAlc, were developed using data from the Swiss Kidney Project on Genes in Hypertension (SKIPOGH) (N = 689). Epigenetic and phenotypic data available from the 1921 (N = 550) and 1936 (N = 1091) Lothian Birth Cohort (LBC) studies, and two publicly available datasets on GEO Accession (GSE50660, N = 464; and GSE110043, N = 94) were used to validate the signatures. A multivariable logistic regression model, adjusting for age and sex, was used to assess the association between self-reported tobacco or alcohol consumption and the respective epigenetic signature, as well as to estimate the association between CVD and epigenetic signatures. A Cox proportional hazard model was used to estimate the risk of mortality in association with the EpiTob and EpiAlc signatures.\nRESULTS: The EpiTob signature was positively associated with self-reported tobacco consumption for current or never smokers with explained variance ranging from 0.49 (LBC1921) to 0.72 (LBC1936) (pseudo-R2). In the SKIPOGH, LBC1921 and LBC1936 cohorts, the epigenetic signature for alcohol consumption explained limited variance in association with self-reported alcohol status [i.e., non-drinker, moderate drinker, and heavy drinker] (pseudo-R2 = 0.05, 0.03 and 0.03, respectively), although this improved considerably when measuring self-reported alcohol consumption with standardized units consumed per week (SKIPOGH R2 = 0.21; LBC1921 R2 = 0.31; LBC1936 R2 = 0.41). Both signatures were associated with history of CVD in SKIPOGH and LBC1936, but not in LBC1921. The EpiTob signature was associated with increased risk of all-cause and lung-cancer specific mortality in the 1936 and 1921 LBC cohorts.\nCONCLUSIONS: This study found the EpiTob and EpiAlc signatures to be well-correlated with self-reported exposure status and associated with long-term health outcomes. Epigenetic signatures of lifestyle exposures may reduce measurement issues and biases and could aid in risk stratification for informing early-stage targeted interventions.", "claims": [{"id": "claim-method", "statement": "Logistic regression models were used to investigate the association between EpiTob and EpiAlc and CVD, individually.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36443762", "locator": "sections[9] \"Statistical analyses\" paragraph 3", "quote": "Logistic regression models were used to investigate the association between EpiTob and EpiAlc and CVD, individually."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data for the SKIPOGH cohort is available upon formal request submitted to the SKIPOGH steering committee (https://www.maelstrom-research.org/study/skipogh). Data for both LBC studies are available upon formal request, additional information can be found on the website: https://www.ed.ac.uk/lothian-birth-cohorts/data-access-collaboration. All epigenetic signatures are available upon request for non-commercial use by contacting genknowme at labo@genknowme.com.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36443762", "locator": "sections[28] \"notes\" paragraph 1", "quote": "Data for the SKIPOGH cohort is available upon formal request submitted to the SKIPOGH steering committee (https://www.maelstrom-research.org/study/skipogh). Data for both LBC studies are available upon formal request, additional information can be found on the website: https://www.ed.ac.uk/lothian-birth-cohorts/data-access-collaboration. All epigenetic signatures are available upon request for non-commercial use by contacting genknowme at labo@genknowme.com."}], "state": "complete"}, {"id": "claim-target-result", "statement": "When adjusting for age, sex, BMI, self-reported drinking status and education, a one standard deviation increase in the EpiTob signature was associated with a 31% higher odds of CVD in the SKIPOGH cohort (OR = 1.31, 95% CI 1.04–1.64), and a 16% increased odds in the LBC1936 cohort, albeit not significant (OR = 1.16, 95% CI 0.99–1.35).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36443762", "locator": "sections[14] \"Association with cardiovascular disease\" paragraph 2", "quote": "When adjusting for age, sex, BMI, self-reported drinking status and education, a one standard deviation increase in the EpiTob signature was associated with a 31% higher odds of CVD in the SKIPOGH cohort (OR = 1.31, 95% CI 1.04–1.64), and a 16% increased odds in the LBC1936 cohort, albeit not significant (OR = 1.16, 95% CI 0.99–1.35)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "When adjusting for age, sex, BMI, self-reported drinking status and education, a one standard deviation increase in the EpiTob signature was associated with a 31% higher odds of CVD in the SKIPOGH cohort (OR = 1.31, 95% CI 1.04–1.64), and a 16% increased odds in the LBC1936 cohort, albeit not significant (OR = 1.16, 95% CI 0.99–1.35).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36443762"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE110043"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE110043"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36443762", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s13148-022-01376-7", "sha256": "sha256:d250c7213bffa0f2cfc592ee7e1b1c777464ed5d347ed6f7a87facff0e1e5460", "bytes": 44488, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s13148-022-01376-7", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9706852", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE110043", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE110043", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE110043", "version": null, "note": "Data for the SKIPOGH cohort is available upon formal request submitted to the SKIPOGH steering committee (https://www.maelstrom-research.org/study/skipogh). Data for both LBC studies are available upon formal request, additional information can be found on the website: https://www.ed.ac.uk/lothian-birth-cohorts/data-access-collaboration. All epigenetic signatures are available upon request for non-commercial use by contacting genknowme at labo@genknowme.com.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data for the SKIPOGH cohort is available upon formal request submitted to the SKIPOGH steering committee (https://www.maelstrom-research.org/study/skipogh). Data for both LBC studies are available upon formal request, additional information can be found on the website: https://www.ed.ac.uk/lothian-birth-cohorts/data-access-collaboration. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE50660", "GSE110043"], "resolved_accessions": ["GSE50660", "GSE110043"], "statements": ["Data for the SKIPOGH cohort is available upon formal request submitted to the SKIPOGH steering committee (https://www.maelstrom-research.org/study/skipogh). Data for both LBC studies are available upon formal request, additional information can be found on the website: https://www.ed.ac.uk/lothian-birth-cohorts/data-access-collaboration. All epigenetic signatures are available upon request for non-commercial use by contacting genknowme at labo@genknowme.com."], "basis": "The paper names GSE50660, GSE110043 in Gene Expression Omnibus and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["glm_logit_fit"], "assets": ["source:pmid:36443762", "data:geo:GSE110043"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE110043"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:17:27Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11724, "completion_tokens": 2600, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:36443762", "type": "paper", "label": "pmid:36443762"}, {"id": "source:pmid:36443762", "type": "manuscript", "label": "PMID 36443762 full text"}, {"id": "data:geo:GSE110043", "type": "dataset", "label": "GEO GSE110043"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36443762", "type": "paper", "label": "pmid:36443762"}, {"id": "source:pmid:36443762", "type": "manuscript", "label": "PMID 36443762 full text"}, {"id": "data:geo:GSE110043", "type": "dataset", "label": "GEO GSE110043"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36443762", "type": "extraction", "used": ["source:pmid:36443762"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE110043", "type": "accession_resolution", "used": ["data:geo:GSE110043"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:36443762", "parent_hash": "sha256:765a1a89ce18c3fbfe0efef619b39065765c20e299cf6e6212e8c043416b3e30", "fork_of": null, "generation": 1}, "gaps": ["asset:data:geo:GSE110043 licence not read", "asset:data:geo:GSE110043 not downloaded", "asset:data:geo:GSE50660 licence not read", "asset:data:geo:GSE50660 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "regression_modelling", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["glm_logit_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Logistic regression models were used to investigate the association between EpiTob and EpiAlc and CVD, individually."], "order_basis": "analysis_only", "id": "assay:1"}]}